engleski

Spindle chirality dynamics during mitosis

Mitotic spindle, a micro-structure responsible for division of the genetic material, consists of two poles, microtubule bundles extending between the poles, and a large number of associated proteins. During spindle formation, microtubule bundles adopt a ‘spindle’ shape, while navigating chromosomes to properly orientate within it. As we previously showed, the spindle shape in human cells is chiral as bundles follow a left-handed helical path, and this chirality can be abolished by inactivation of the motor protein Eg5/kinesin- 5 [1]. However, it is not known how chirality changes throughout mitosis, how other microtubule- associated proteins affect it, and to what extent it is conserved. Here we show that spindles have larger values of left-handed helicity in very late metaphase and early anaphase, compared to values during spindle formation, i.e., prometaphase and metaphase plate formation. Furthermore, we tested other motor and non-motor proteins that could be involved in spindle chirality. Among the candidate microtubule-associated proteins, we found that depletion of PRC1 or Kif18A/kinesin- 8 lead to a decrease of left-handed helicity, suggesting the role of these proteins in producing or maintaining spindle chirality. Finally, we show that spindle chirality is present in other organisms, specifically in the amoeba Naegleria fowleri. Although this organism has a spindle that is much different than those in human cells, microtubule bundles still adopt a helical form. Surprisingly, the bundles in amoebas typically follow a right- handed helical path. In the future, it will be interesting to see why spindle chirality is more pronounced around anaphase onset and what role it may have in chromosome segregation. [1] M. Novak, B. Polak, J. Simunić, Z. Boban, B. Kuzmić, A.W. Thomae, I.M. Tolić, N. Pavin, The mitotic spindle is chiral due to torques within microtubule bundles, Nat. Commun., 9(1):3571 (2018)

Mitotic spindle ; chirality ; twist ; helicity ; motor proteins

nije evidentirano